Bottom Line:
In this study, we examined the dependence potential and abuse liability of tramadol as well as its effect on the dopaminergic and serotonergic systems in rodents.In animal behavioral tests, tramadol did not show any positive effects on the experimental animals in climbing, jumping, and head twitch tests.However, in the conditioned place preference and self-administration tests, the experimental animals showed significant positive responses.

Affiliation: Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Chungju 361-709 ; Department of Infectious Diseases, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Republic of Korea.

ABSTRACTTramadol is an opioid analgesic agent that has been the subject of a series of case reports suggesting potential for misuse or abuse. However, it is not a controlled substance and is not generally considered addictive in Korea. In this study, we examined the dependence potential and abuse liability of tramadol as well as its effect on the dopaminergic and serotonergic systems in rodents. In animal behavioral tests, tramadol did not show any positive effects on the experimental animals in climbing, jumping, and head twitch tests. However, in the conditioned place preference and self-administration tests, the experimental animals showed significant positive responses. Taken together, tramadol affected the neurological systems related to abuse liability and has the potential to lead psychological dependence.

Mentions:
The jumping test was performed to determine if tramadol showed withdrawal syndrome. We administered the saline (1 mg/kg, i.p.) or one of three doses of tramadol (0.03, 0.07, or 0.1 mg/kg, i.p.) prior to administering morphine. The mice received morphine (150 mg/kg, subcutaneously) 4 hr before naloxone (10 mg/kg, i.p.). As shown in Fig. 2, two groups of tramadol-treated mice (0.03 and 0.07 mg/kg) showed the jumping behavior, but the difference between the saline-treated group and tramadol-treated group was not significant. In the morphine-pretreated groups, two of tramadol-treated groups jumped more than saline-treated group; one tramadol-treated group showed a statistically significant increase (0.03 mg/kg). The results are depicted in Fig. 2.

Mentions:
The jumping test was performed to determine if tramadol showed withdrawal syndrome. We administered the saline (1 mg/kg, i.p.) or one of three doses of tramadol (0.03, 0.07, or 0.1 mg/kg, i.p.) prior to administering morphine. The mice received morphine (150 mg/kg, subcutaneously) 4 hr before naloxone (10 mg/kg, i.p.). As shown in Fig. 2, two groups of tramadol-treated mice (0.03 and 0.07 mg/kg) showed the jumping behavior, but the difference between the saline-treated group and tramadol-treated group was not significant. In the morphine-pretreated groups, two of tramadol-treated groups jumped more than saline-treated group; one tramadol-treated group showed a statistically significant increase (0.03 mg/kg). The results are depicted in Fig. 2.

Bottom Line:
In this study, we examined the dependence potential and abuse liability of tramadol as well as its effect on the dopaminergic and serotonergic systems in rodents.In animal behavioral tests, tramadol did not show any positive effects on the experimental animals in climbing, jumping, and head twitch tests.However, in the conditioned place preference and self-administration tests, the experimental animals showed significant positive responses.

Affiliation:
Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Chungju 361-709 ; Department of Infectious Diseases, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Republic of Korea.

ABSTRACTTramadol is an opioid analgesic agent that has been the subject of a series of case reports suggesting potential for misuse or abuse. However, it is not a controlled substance and is not generally considered addictive in Korea. In this study, we examined the dependence potential and abuse liability of tramadol as well as its effect on the dopaminergic and serotonergic systems in rodents. In animal behavioral tests, tramadol did not show any positive effects on the experimental animals in climbing, jumping, and head twitch tests. However, in the conditioned place preference and self-administration tests, the experimental animals showed significant positive responses. Taken together, tramadol affected the neurological systems related to abuse liability and has the potential to lead psychological dependence.